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Colorectal cancer (CRC) ranks third in global incidence and second in mortality. However, a comprehensive predictive model for CRC prognosis, immunotherapy response, and drug sensitivity is still lacking. Various types of programmed cell death (PCD) are crucial for cancer occurrence, progression, and treatment, indicating their potential as valuable predictors. Fourteen PCD genes were collected and subjected to dimensionality reduction using regression methods to identify key hub genes. Predictive models were constructed and validated based on bulk transcriptomes and single-cell transcriptomes. Furthermore, the tumor microenvironment, immunotherapy response, and drug sensitivity profiles among patients with CRC were explored and stratified by risk. A risk score incorporating the PCD genes FABP4, AQP8, and NAT1 was developed and validated across four independent datasets. Patients with CRC who had a high-risk score exhibited a poorer prognosis. Unsupervised clustering algorithms were used to identify two molecular subtypes of CRC with distinct features. The risk score was combined with the clinical features to create a nomogram model with superior predictive performance. Additionally, patients with high-risk scores exhibited decreased immune cell infiltration, higher stromal scores, and reduced responsiveness to immunotherapy and first-line clinical drugs compared with low-risk patients. Furthermore, the top ten non-clinical first-line drugs for treating CRC were selected based on their predicted IC50 values. Our results indicate the efficacy of the model and its potential value in predicting prognosis, response to immunotherapy, and sensitivity to different drugs in patients with CRC. [ABSTRACT FROM AUTHOR]

Global change factors, such as variation in precipitation regimes and nitrogen (N) deposition, are likely to occur simultaneously and may have profound impacts on the relative abundance of grasses differing in functional traits, such as C3 and C4 species. We conducted an extreme drought and re-watering experiment to understand differences in the resistance and recovery abilities of C3 and C4 grasses under different N deposition scenarios. A C3 perennial grass (Leymus chinensis) and two C4 grasses (annual species Chloris virgata and perennial species Hemarthria altissima) that co-occur in Northeast China were selected as experimental plants. For both C3 and C4 grasses, N addition caused a strong increase in biomass and resulted in more severe drought stress, leading to a change in the dominant photosynthetic limitation during the drought periods. Although N addition increased antioxidant enzyme activities and protective solute concentrations, the carbon fixing capacity did not fully recover to pre-drought levels by the end of the re-watering period. N addition resulted in lower resilience under the drought conditions and lower resistance at the end of the re-watering. However, N addition led to faster recovery of photosynthesis, especially in the C3 grass, which indicate that the effect of N addition on photosynthesis during drought was asymmetric, especially in the plants with different photosynthetic nitrogen use efficiency (PNUE). These findings demonstrated that nitrogen deposition may significant alter the susceptibility of C3 and C4 grass species to drought stress and re-watering, highlighting the asymmetry between resistance and resilience and to improve our understanding about plant responses to climate change.